466 results about "Autophagy" patented technology

The invention discloses a construction method for a Sqstm1 whole-genome knockout mouse animal model and application. The mouse animal model is a mouse of which the Sqstm1 gene is knocked out. On the basis of a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 gene knockout technology, the Sqstm1 gene knockout mouse model is constructed. The construction method comprises the following steps: S1: designing sgRNA (Ribonucleic Acid) and Cas9 RNA, carrying out in vitro transcription to obtain mRNA, carrying out microinjection on the sgRNA and the Cas9 RNA with activity into amouse oosperm, to obtain the Sqtm1 gene knockout mouse; S2: identifying the Sqtm1 gene knockout mouse animal model. On the basis of the CRISPR/Cas9 gene knockout technology, the Sqstm1 gene knockout mouse animal model is constructed for the first time, and a convenient, reliable and economic animal model is provided for researching a relationship between Sqstm1 and diseases including autophagy, tumors and the like.

A method for inhibiting the autophagy of motor neurons in a subject is provided. The method comprises administrating to the subject an effective amount of an active ingredient selected from the group consisting of a compound of formula (I), a pharmaceutically acceptable salt of the compound, a pharmaceutically acceptable ester of the compound and combinations thereof:

wherein A is a C1-C5 alkyl optionally having one or more unsaturated bonds and optionally being substituted by one or more substituents selected from a group consisting of —OH, ═O and C1-C3 alkyl; X is H, —OH,

Y is O or S and can optionally combine with A to form a five-membered ring; and R₁ is H or a substituted or unsubstituted C1-C20 alkyl, wherein one or more —CH₂— of the C1-C20 alkyl are optionally being replaced by —NH— or —O—.

The invention belongs to the field of biomedical science, and aims to provide a high metastatic potential hepatoma cell line capable of steady autophagy indication, and an establishment method and an application method thereof. Lentivirus expression vectors containing EGFP (enhanced green fluorescent protein)-LC3 (light chain 3) autophagy reporter genes are constructed and used to infect hepatoma cells with high metastatic potential, so that host cells can express the EGFP-LC3 steadily and efficiently and indicate autophagy changes of the hepatoma cells steadily. To apply the cell line, metastasis research models can be established in vitro and in vivo for the observation on autophagy changes during metastasis, and the cell autophagy changes can be analyzed rapidly and quantitatively by adopting an image analysis method based on Top-hat operators and morphological filter. The high metastatic potential hepatoma cell line has the characteristics that autophagy indication is conducted steadily, reliably and sensitively in a real-time manner, the metastasis occurs definitely, the autophagy is quantified rapidly and accurately, the operation is simple and convenient, and the like, and can greatly facilitate correlation study on autophagy and metastasis.

The present disclosure relates to methods for the modulation of autophagy and the treatment of autophgy-related diseases, including cancer, neurodegenerative diseases and pancreatitis.

A method for inducing autophagy in a subject having an autophagy defect is provided. The method of the present invention includes the step of administering to the subject a therapeutically effective amount of a Ganoderma lucidum extract, wherein the autophagy enhances clearance of protein aggregates in the subject.

The invention relates to a clinic detection marker of an inflammatory bowel disease, and applications thereof, and concretely relates to a molecular marker-Erbin gene in the inflammatory bowel disease, and an application of an inhibitor chloroquine of a downstream autophagy pathway regulated by the marker. An experiment result shows that the intestinal mucosa damage of DSS induced Erbin<+/+> and Erbin<-/-> mice injected with chloroquine are substantially reduced, the intestinal mucosa damage of the Erbin<-/-> mice is obviously severer than that of the Erbin<+/+> mice, and the mice injected with chloroquine have higher intestinal mucosa integrity, substantially lower inflammatory cell infiltration and substantially alleviated inflammatory bowel disease symptoms than mice not injected with the chloroquine, so the autophagy inhibitor chloroquine can improve the integrity of the intestinal mucosa and has a very good IBD inhibition effect, thereby the chloroquine has certain prevention and treatment effects on the inflammatory bowel disease.

This invention provides compositions and method of diminishing or inhibiting autophagy by administering a FLIP protein that binds to Atg3, interfering with the formation of the LC3-Atg4-Atg7-Atg3 conjugation complex necessary for autophagy induction. This invention also provides FLIP peptide fragments that promote or induce autophagy by interfering with the activity of FLIP.

The invention provides application of dihydroartemisinin to preparation of a tumor cell autophagy induction medicament. The molecular formula of the dihydroartemisinin is C15H24O5. The medicinal preparation comprises a preparation-allowable medicinal excipient or carrier. The excipient is in the form of a solid preparation. The medicinal preparation provided by the invention can be used as a mitochondrion targeting autophagy inductor, which has a specific anti-tumor effect and can provide a therapeutic medicament for overcoming medicament resistance and improving prognosis for treatment of tumors. The effects and the mechanisms of effective monomer components in a traditional Chinese medicine are research and described under the background of a cell autophagy theory; and an important basis is provided for the development of new theory of the traditional Chinese medicine and new acting target of the medicament, and a new research direction for developing the theory of the traditional Chinese medicine is provided.

The invention discloses a method for promoting induced pluripotent stem cells to induce and differentiate to be nerve cells, which comprises steps: induced pluripotent stem (iPS) cells are blown and absorbed to disperse to be single cell suspension after being digested, and are separately planted in culture holes, and rock (ROCK) inhibitors are added into each culture hole; a supernate is adsorbed to discard in the first day after the iPS cells are separately planted, is added into a neural induction complete culture medium, and rapamycin needs to be added into the neural induction complete culture medium to promote autophagy; the neural induction complete culture medium is changed to add low concentration rapamycin to promote autophagy neural cells to differentiate the neural induction complete culture medium after two days, and can be induced to differentiate to be neural cells after being cultured for 12-15 days. The method for promoting the induced pluripotent stem cells to induce and differentiate to be the nerve cells can speed up neurons to induce and differentiate, and improves neuron growth states ofspinocerebellum ataxic three-type iPS.

The present invention belongs to the technical field of medicine and biology, and relates to an antitumor drug synergism drug, particularly to a tumor treatment synergism drug composition comprising an autophagy inhibitor and adriamycin. The combination drug comprises one or a plurality of autophagy inhibitors and adriamycin, and is provided for treating tumors by adopting a combination administration or sequential use mode, wherein tumor cell autophagy induced by adriamycin can be inhibited to counteract antagonism effects of tumors on treatments of adriamycin due to autophagy so as to significantly enhance tumor treatment effects of adriamycin. The synergism drug composition is suitable for treatment of lymphoma, lung cancers, brain tumors, breast cancers and myeloma.

A method for producing a plant with increased yield as compared to a corresponding wild type plant whereby the method comprises at least the following step: increasing or generating in a plant or a part thereof one or more activities of a polypeptide selected from the group consisting of 26S proteasome-subunit, 50S ribosomal protein L36, Autophagy-related protein, B0050-protein, Branched-chain amino acid permease, Calmodulin, carbon storage regulator, FK506-binding protein, gamma-glutamyl-gamma-aminobutyrate hydrolase, GM02LC38418-protein, Heat stress transcription factor, Mannan polymerase II complex subunit, mitochondrial precursor of Lon protease homolog, MutS protein homolog, phosphate transporter subunit, Protein EFR3, pyruvate kinase, tellurite resistance protein, Xanthine permease, and YAR047C-protein.

The present disclosure provides methods and compositions comprising a autophagy inhibitors. Also provided herein are autophagy inhibitors for use as a contraceptive device. Also provided are autophagy inhibitors delivered by an intrauterine delivery system (IUS) to prevent pregnancy or provide contraception. Also provided herein are newly identified compositions for use as autophagy inhibitors.

Methods and compounds are disclosed for wound healing by modulating autophagy. A formulation for modulating autophagy comprises a first modulating compound (FAM) selected from compounds having the general structure (I):

An electromagnetic field generating apparatus for treating pathological cells, in particular with tumor suppression function. The ratio of static magnetic field to alternating magnetic field is in the range of 0.5-2.5, and the total intensity is in the range up to 100 mT. It provides non-invasive low toxicity and side effects, significantly inhibiting a plurality of tumors, influencing the intracellular superoxide radical content, and promoting cell autophagy. The mechanism of action of the magnetic field is on the electron spin energy levels and consequently on the free radicals concentration. Additional magnetic field having frequency up to 100 MHz and intensity down to microTesla range can be also used to improve the antitumor efficacy in combination with the static as well as the extremely low frequency electromagnetic field (1-300 Hz) influencing the spin hyperfine resonance. A combination method is also provided of a power-frequency electromagnetic field generating device and a platinum-based medicine. The in vitro and in vivo experiments confirmed that the tumor therapeutic electromagnetic field combined with platinum-based chemotherapy drugs can enhance the efficacy of platinum-based chemotherapy drugs and magnetic field alone, a significant inhibition of a variety of tumors; can reduce the dose of cisplatin and reduce side effects.

The present invention provides novel methods for the modulation of autophagy and the treatment of autophagy-related diseases, including cancer, neurodegenerative diseases, liver diseases, muscle diseases and pancreatitis.

The invention relates to antitumor drugs and discloses anti-glioma drugs based on Venenum Bufonis extract and a preparation method thereof, the drugs being a bufotalin submicron emulsion and a bufotalin nanoparticle preparation, wherein the bufotalin submicron emulsion comprises Venenum Bufonis extract, medium chain triglyceride, a lecithin, poloxamer 188, glycerol, sodium oleate and injection water; the bufotalin nanoparticle preparation comprises Venenum Bufonis extract, glycerol monostearate, medium-chain fatty acid glyceride, oleic acid, a lecithin, poloxamer 188, sodium deoxycholate and injection water. Both the two preparations can combine with endothelial cells in cerebral blood capillaries, enabling the drugs to be transmitted into the brain through membranes or by means of adsorption, medication, endocytosis and transferring, cerebral targeting of the drugs is improved, and further increase of bufotalin in the brain is facilitated, and glioma resistance is achieved by inducing apoptosis and excessive autophagy of cells.

The invention provides new application for a lycorine and bortezomib composition medicine. The lycorine and bortezomib composition is used for preparing a medicinal preparation for treating multiple myeloma. Compared with the fact that lycorine and bortezomib are used separately, combined use of lycorine and bortezomib can realize a better cell proliferation inhibition effect, and cell autophagy can be inhibited through combined use. The composition greatly improves sensibility of multiple myeloma to bortezomib and is applicable to drug-resistant multiple myeloma which is difficult to treat.

The invention belongs to the technical field of medicines, in particular relates to a physalin A extracting process and medical application thereof, in particular relates to a novel application of physalin A in preparation of an anti-tumor dug and in particular relates to the use of physalin A in treatment of human fibrosarcoma and human malignant melanoma. After process optimization, the extracting rate of physalin A is 0.2133%. Physalin A can be used for inhibiting the growth of various tumor cells, particularly has obvious inhibiting action on the growth of the human fibrosarcoma and human malignant melanoma, but does not inhibit the activities of the human normal cells obviously. The mechanism is that the downstream caspase family-associated protein is activated by activating Fas death receptors, so that the tumor cells are induced to generate apoptosis. Meanwhile, the physalin A can be used for inducing the tumor cells to generate autophagy for achieving autophagy antagonism apoptosis in the HT1080 and the A375-S2 cells; and the p53 protein and the MAPK (Mitogen-Activated Protein Kinase)-familty p38 protein have a key regulation effect. The physalin A can be used for preparing a digestive tract dosage form or a non-digestive tract dosage form, which can be used for treating tumors including the human fibrosarcoma and human malignant melanoma.

The invention relates to a micromolecule compound having the functions of anti-tumor and autophagy, a preparation method and the application thereof. The micromolecule compound is a manganese complex L<1>MnCl2 and L<2>MnCl, wherein, the L<1> represents 2-double pyridine methyl-amine propionic ether; and the L<2> represents 2-double pyridine methyl-amine monoprop. The micromolecule compound is obtained through chemosynthesis by taking the ligand L<1> or L<2> and the MnCl2 as main materials. The manganese complex of the double pyridine methyl-amine ligand has strong inhibition effects on the growth of tumor cells A549, Hela, HepG-2 and Eca109, can inhibit the swelling of the mitochondrial induced by the calcium ion and induce the apoptosis of the tumor cells by means of autophagy; the micromolecule compound can be taken as new anti-tumor activity medicine which takes the mitochondria as target spot and the tumor cell autophagy agent used for the drug tolerance tumor therapy.